Education
- Dr. rer. nat., University of Bremen, Germany, 1989
- M.S., University of Bremen, 1986
Areas of Interest
Nucleosides for anticancer, antiviral, and antibiotic therapies
Nucleoside antimetabolites such as gemcitabine, cytarabine, cladribine, fludarabine, clofarabine, acyclovir, ganciclovir, brivudine, zidovudine, stavudine, and emtricitabine are prodrugs that are widely used as anticancer agents or antiviral agents and their importance continues to increase. These antimetabolites utilize nucleoside salvage pathways for their transformation into active nucleoside triphosphates. Irrespective of the final intracellular targets of the triphosphates, which primarily are human or viral DNA and their respective polymerases or reverse transcriptases, the rate-limiting key activation step of the prodrugs is usually the initial conversion of the nucleoside to the corresponding monophosphate by phosphorylating enzymes, often deoxynucleoside kinases. Thymidine kinase (TK) is one of these deoxynucleoside kinases. Most eukaryotes and prokaryotes and many DNA viruses code for proteins with thymidine kinase activity. However, among all approved nucleoside antimetabolites only the HIV prodrugs zidovudine and stavudine are activated by human thymidine kinase 1 (hTK1). This is probably due to the fact that TKs have the most stringent substrate specificity among all nucleoside kinases and that crystal structures for drug design have only become available very recently. Dr. Tjarks’ research activities focus on the in silico design, synthesis, and biological evaluation of inhibitors and substrates of TKs from e.g. Bacillus anthracis and Epstein-Barr virus as well as from hTK1 for antibiotic, antiviral, and anticancer therapies.
A second research focus of Dr. Tjarks’ group is the synthesis of boron and lanthanide containing porphyrin-type macrocycles, which could be considered as “multipurpose” anticancer diagnostics and therapeutics. Due to their unique intrinsic properties boron/lanthanide containing porphyrin-type macrocycles could serve as MRI contrast agents, near-infrared imaging agents, neutron capture therapy (NCT) agents, radiationsensitizer, photosensitizer, and cancer chemotherapeutics.
A third research focus of Dr. Tjarks' group is the synthesis of boron and gadolinium containing compounds that are utilized for the construction of tumor-targeted liposomes and nanoparticles for Neutron Capture Therapy of Cancer. Targeted cellular receptors include the vascular endothelial growth factor receptor (VEGFR), the epithelial growth factor receptor (EGFR), and the folate receptor (FR).
Publications
- Bandyopadhyaya, A. K.; Narayanasamy, S.; Barth, R.F.; Tjarks, W.; Synthesis of novel texaphyrins containing lanthanides and boron; Tetrahedron Lett., 48, 4467-4469, 2007.
- Wu, W.; Yang, W.; Barth, R.F.; Kawabata, S.; Swindall, M.; Bandyopadhyaya, A.K.; Tjarks, W.; Khorsandi, B.; Blue, T.E.; Ferketich, A.F.; Yang, M.; Christoforidis, G.A.; Sferra, T.J.; Binns, P.J.; Riley, K.J.; Ciesielski, M.J.; Fenstermaker, R.A. Molecular targeting and treatment of an EGF receptor positive glioma using boronated cetuximab. Clin. Cancer Res. 13, 1260-1268, 2007.
- Pan, X.; Wu, G.; Yang, W.; Barth, R.F.; Tjarks, W.; Lee, R. J.; Synthesis of Cetuximab-Immunoliposomes via a Cholesterol-Based Membrane Anchor for Targeting of EGFR, Bioconjugate. Chem., 18, 101-108, 2007.
- Carnrot, C.; Vogel, S.R.; Byun, Y.; Wang, L.; Tjarks, W.; Eriksson, S.; Phipps, A.J.; Evaluation of Thymidine Kinase as a Potential Target for Development of Nucleoside Analogs against Bacillus anthracis; Biol. Chem., 387, 1575-1581, 2006.
- Thirumamagal, B.T.S., Zhao, X. B.; Bandyopadhyaya, A.K.; Johnsamuel, J.; Tiwari, R.V.; Golightly, D.W., Patel, V.; Jehning, B.T.; Backer, M.V.; Backer, J.M.; Lee, R.J.; Barth, R.F.; Tjarks, W.; Liposomal Formulations of Boron-Containing Cholesterol Mimics for Boron Neutron CaptureTherapy (BNCT); Bioconjugate. Chem., 1141-1150, 2006.
- Byun, Y; Thirumamagal, B.T.S.; Yang, W.; Eriksson, S.; Barth, R.F.; Tjarks, W. ; Preparation and Biological Evaluation of 10B-Enriched N5-2OH: A Promising Boron Delivery Agent for Boron Neutron Capture Therapy (BNCT) of Brain Tumors; J. Med. Chem., 49, 5513-5523, 2006.
- Bandyopadhyaya, A.K.; Tiwari, R.V.; Tjarks, W.; Comparative Molecular Field Analysis and Comparative Molecular Similarity Indices Analysis of Boron Containing Human Thymidine Kinase 1 Substrates, Bioorg. Med. Chem., 14, 6924-6932, 2006.
- Narayanasamy, S.; Thirumamagal, B.T.S.; Johnsamuel, J.; Carnrot, C.; Byun, Y.; Cosquer, G.Y.; Yan, J.; Bandyopadhyaya, A.K.; Tiwari, R.V.; Eriksson. S.; Tjarks, W. Hydrophilically-Enhanced 3-Carboranyl Thymidine Analogues (3CTAs) for Boron Neutron Capture Therapy (BNCT) of Cancer, Bioorg. Med. Chem., 14, 6886 -6899, 2006.
- Byun, Y., Tjarks, W.; Investigation of Zwitterionic 7-Ammomium-7,9-nido-m-Carborane. Tetrahedron Lett., 47, 5649-5652, 2006.
- Yang, W.; Barth, R.F.; Wu, G.; Kawabata, S.; Sferra, T. J.; Bandyopadhyaya, A.K.; Tjarks, W.; Ferketich, A.K.; Binns, P.J.; Riley, K.J.; Coderre, J.A.; Ciesielski, M.J.; Robert A. Fenstermaker, R.A.; and Carol J. Wikstrand, C.J.; Molecular Targeting and Treatment of EGFRvIII Positive Gliomas Using Boronated Monoclonal Antibody L8A4, Clin. Cancer Res., 12, 3792-3802, 2006.
Courses Taught
- Pharmacy 410: Introduction to Medicinal Chemistry (team-taught course).
- Pharmacy 605: Drug-receptor/enzyme interactions, drug design concepts, acidity and basicity of drugs, physicochemical properties and metabolism of drugs. Chemical and biochemical principles governing the properties of drugs. Drug categories include: Analgesics, anesthetics, CNS depressants, CNS stimulants, cholinergics, adrenergics, and drugs for the treatment of neurodegenerative diseases.
- Pharmacy 606 : Chemical and biochemical principles governing the properties of drugs. Drug categories include: Antihypertensives, antianginal, antiarrhythmics, anticoagulants, agents for congestive heart failure, antihistaminmes and antidiabetics (team-taught course).
- Pharmacy 607: Chemical and biochemical principles governing the properties of drugs. Drug categories include: Steroid hormones such as androgens, antiandrogens, estrogen and antiestrogens, adrenocorticoids, prostaglandins and NSAIDs agents, anticancer agents and antiviral agents. (team-taught course).
- Pharmacy 735: A study of the discovery and design of new drugs; topics include natural products isolation, molecular modeling, molecular targets, and biosynthesis and metabolism (team-taught course).
- Pharmacy 807: Targeted drug delivery systems for cancer and leukemia (team-taught course).
- Pharmacy 836: Selected topics in medicinal chemistry, the subject matter being drawn from the current literature (team-taught course).
- Pharmacy 837: Discovery, development, and mechanisms of action of drugs used to treat bacterial, fungal, viral, and parasitic infections (team-taught course).
Professional Experience
- 2007-present: Associate Professor, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
- 2001-2007: Assistant Professor, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
- 2000-2001: Adjunct Assistant Professor, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
- 1997-2001: Research Scientist, Division of Medicinal Chemistry & Pharmacognosy,
College of Pharmacy, The Ohio State University, Columbus, OH
- 1994-1996: Research Associate, Department of Organic Chemistry, Uppsala University, Sweden
- 1990-1993: Postdoctoral Researcher, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
- 1986-1990: Research Associate, Department of Chemistry & Biology, University of Bremen, Germany
